Dr. Chole's laboratory is interested in the cellular and molecular mechanisms of localized bone remodeling in the middle ear. Bone in the middle ear is normally quiescent, but extensive remodeling can be induced by disease states like cholesteatoma. We are particularly interested in the modulatory role of signaling molecules such as nitric oxide and interleukin-1. Our preliminary data suggests that Cytochrome P450 may represent an alternate, or even preferred pathway to nitric oxide production in bone. Nitric oxide is an important regulator of osteoclast activity. This proposal outlines studies to further elucidate the role of Cytochrome P450 in the modulation of nitric oxide signaling in bone.